Quantifying Hand Strength and Isometric Pinch Individuation Using a Flexible Pressure Sensor Grid.

Modulating force between the thumb and another digit, or isometric pinch individuation, is critical for daily tasks and can be impaired due to central or peripheral nervous system injury. Because surgical and rehabilitative efforts often focus on regaining this dexterous ability, we need to be able to consistently quantify pinch individuation across time and facilities. Currently, a standardized metric for such an assessment does not exist. Therefore, we tested whether we could use a commercially available flexible pressure sensor grid (Tekscan F-Socket [Tekscan Inc., Norwood, MA, USA]) to repeatedly measure isometric pinch individuation and maximum voluntary contraction (MVC) in twenty right-handed healthy volunteers at two visits. We developed a novel equation informed by the prior literature to calculate isometric individuation scores that quantified percentage of force on the grid generated by the indicated digit. MVC intra-class correlation coefficients (ICCs) for the left and right hands were 0.86 (p < 0.0001) and 0.88 (p < 0.0001), respectively, suggesting MVC measurements were consistent over time. However, individuation score ICCs, were poorer (left index ICC 0.41, p = 0.28; right index ICC -0.02, p = 0.51), indicating that this protocol did not provide a sufficiently repeatable individuation assessment. These data support the need to develop novel platforms specifically for repeatable and objective isometric hand dexterity assessments.

Quantitative assessments of finger individuation with an instrumented glove.

BACKGROUND: In clinical and research settings, hand dexterity is often assessed as finger individuation, or the ability to move one finger at a time. Despite its clinical importance, there is currently no standardized, sufficiently sensitive, or fully objective platform for these evaluations. METHODS: Here we developed two novel individuation scores and tested them against a previously developed score using a commercially available instrumented glove and data collected from 20 healthy adults. Participants performed individuation for each finger of each hand as well as whole hand open-close at two study visits separated by several weeks. Using the three individuation scores, intra-class correlation coefficients (ICC) and minimal detectable changes (MDC) were calculated. Individuation scores were further correlated with subjective assessments to assess validity. RESULTS: We found that each score emphasized different aspects of individuation performance while generating scores on the same scale (0 [poor] to 1 [ideal]). These scores were repeatable, but the quality of the metrics varied by both equation and finger of interest. For example, index finger intra-class correlation coefficients (ICC's) were 0.90 (< 0.0001), 0.77 (< 0.001), and 0.83 (p < 0.0001), while pinky finger ICC's were 0.96 (p < 0.0001), 0.88 (p < 0.0001), and 0.81 (p < 0.001) for each score. Similarly, MDCs also varied by both finger and equation. In particular, thumb MDCs were 0.068, 0.14, and 0.045, while index MDCs were 0.041, 0.066, and 0.078. Furthermore, objective measurements correlated with subjective assessments of finger individuation quality for all three equations (ρ = - 0.45, p < 0.0001; ρ = - 0.53, p < 0.0001; ρ = - 0.40, p < 0.0001). CONCLUSIONS: Here we provide a set of normative values for three separate finger individuation scores in healthy adults with a commercially available instrumented glove. Each score emphasizes a different aspect of finger individuation performance and may be more uniquely applicable to certain clinical scenarios. We hope for this platform to be used within and across centers wishing to share objective data in the physiological study of hand dexterity. In sum, this work represents the first healthy participant data set for this platform and may inform future translational applications into motor physiology and rehabilitation labs, orthopedic hand and neurosurgery clinics, and even operating rooms.

Synchronization of kinetic and kinematic hand tasks with electrocorticography and cortical stimulation during awake craniotomies.

Awake craniotomies provide unique and invaluable scientific opportunities for neurophysiological experimentation in consenting human subjects. While such experimentation carries a long history, rigorous reporting of methodologies focusing on synchronizing data across multiple platforms is not universally reported and often not translatable to across operating rooms, facilities, or behavioral tasks. Therefore, here we detail an intraoperative data synchronization methodology designed to work across multiple commercially available platforms to collect behavioral and surgical field videos, electrocorticography, brain stimulation timing, continuous finger joint angles, and continuous finger force production. Our technique was developed to be nonobstructive to operating room (OR) staff and generalizable to a variety of hand-based tasks. We hope that the detailed reporting of our methods will support the scientific rigor and reproducibility of future studies, as well as aid other groups interested in performing related experiments.

Mechanisms and therapeutic implications of hypermutation in gliomas.

A high tumour mutational burden (hypermutation) is observed in some gliomas1-5; however, the mechanisms by which hypermutation develops and whether it predicts the response to immunotherapy are poorly understood. Here we comprehensively analyse the molecular determinants of mutational burden and signatures in 10,294 gliomas. We delineate two main pathways to hypermutation: a de novo pathway associated with constitutional defects in DNA polymerase and mismatch repair (MMR) genes, and a more common post-treatment pathway, associated with acquired resistance driven by MMR defects in chemotherapy-sensitive gliomas that recur after treatment with the chemotherapy drug temozolomide. Experimentally, the mutational signature of post-treatment hypermutated gliomas was recapitulated by temozolomide-induced damage in cells with MMR deficiency. MMR-deficient gliomas were characterized by a lack of prominent T cell infiltrates, extensive intratumoral heterogeneity, poor patient survival and a low rate of response to PD-1 blockade. Moreover, although bulk analyses did not detect microsatellite instability in MMR-deficient gliomas, single-cell whole-genome sequencing analysis of post-treatment hypermutated glioma cells identified microsatellite mutations. These results show that chemotherapy can drive the acquisition of hypermutated populations without promoting a response to PD-1 blockade and supports the diagnostic use of mutational burden and signatures in cancer.